Wnt/beta-catenin signaling regulates cranial base development and growth.
Wnt/beta-catenin signaling regulates cranial base development and growth.
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DOI：
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发表时间：
2008
影响因子：
7.6
通讯作者：
M. Nagayama;M. Iwamoto;A. Hargett;N. Kamiya;Y. Tamamura;B. Young;T. Morrison;H. Takeuchi;M. Pacifici;M. Enomoto-Iwamoto;E. Koyama
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作者：
M. Nagayama;M. Iwamoto;A. Hargett;N. Kamiya;Y. Tamamura;B. Young;T. Morrison;H. Takeuchi;M. Pacifici;M. Enomoto-Iwamoto;E. Koyama
Wnt蛋白和β-连环蛋白信号调节胚胎发育过程中的主要过程，我们假设它们调节颅底软骨结合的发育和生长。为了解决这个问题，我们分析了软骨特异性β-连环蛋白缺陷小鼠。突变体软骨结合缺乏典型的生长板区，软骨内骨化延迟。在相互的转基因实验中，组成性活性Lef 1（Wnt/β-连环蛋白信号传导的转录介质）的软骨过表达引起早熟软骨细胞肥大和未成熟和成熟软骨细胞的混合。在β-连环蛋白缺乏的软骨结合中观察到的发育变化伴随着Ihh和PTHrP以及sFRP-1（内源性Wnt信号传导拮抗剂和潜在的Ihh信号传导靶点）的显著降低。因此，Wnt/β-连环蛋白信号传导对于颅底发育和软骨结合生长板功能至关重要。该途径促进软骨细胞成熟和骨化事件，并可能通过抑制Ihh-PTHrP与sFRP-1的作用发挥这一重要作用。
Wnt proteins and beta-catenin signaling regulate major processes during embryonic development, and we hypothesized that they regulate cranial base synchondrosis development and growth. To address this issue, we analyzed cartilage-specific beta-catenin-deficient mice. Mutant synchondroses lacked typical growth plate zones, and endochondral ossification was delayed. In reciprocal transgenic experiments, cartilage overexpression of a constitutive active Lef1, a transcriptional mediator of Wnt/beta-catenin signaling, caused precocious chondrocyte hypertrophy and intermingling of immature and mature chondrocytes. The developmental changes seen in beta-catenin-deficient synchondroses were accompanied by marked reductions in Ihh and PTHrP as well as sFRP-1, an endogenous Wnt signaling antagonist and a potential Ihh signaling target. Thus, Wnt/beta-catenin signaling is essential for cranial base development and synchondrosis growth plate function. This pathway promotes chondrocyte maturation and ossification events, and may exert this important role by dampening the effects of Ihh-PTHrP together with sFRP-1.